1mzf

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{{Seed}}
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{{STRUCTURE_1mzf| PDB=1mzf | SCENE= }}
{{STRUCTURE_1mzf| PDB=1mzf | SCENE= }}
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'''Human Factor inhibiting HIF (FIH1) in Complex with 2-oxoglutarate'''
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===Human Factor inhibiting HIF (FIH1) in Complex with 2-oxoglutarate===
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==Overview==
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Precise regulation of the evolutionarily conserved hypoxia-inducible transcription factor (HIF) ensures proper adaptation to variations in oxygen availability throughout development and into adulthood. Oxygen-dependent regulation of HIF stability and activity are mediated by hydroxylation of conserved proline and asparagine residues, respectively. Because the relevant prolyl and asparginyl hydroxylases use O(2) to effect these posttranslational modifications, these enzymes are implicated as direct oxygen sensors in the mammalian hypoxic response pathway. Here we present the structure of factor-inhibiting HIF-1 (FIH-1), the pertinent asparaginyl hydroxylase involved in hypoxic signaling. Hydroxylation of the C-terminal transactivation domain (CTAD) of HIF by FIH-1 prevents CTAD association with transcriptional coactivators under normoxic conditions. Consistent with other structurally known hydroxylases, FIH-1 is comprised of a beta-strand jellyroll core with both Fe(II) and the cosubstrate 2-oxoglutarate bound in the active site. Details of the molecular contacts at the active site of FIH-1 have been elucidated and provide a platform for future drug design. Furthermore, the structure reveals the presence of a FIH-1 homodimer that forms in solution and is essential for FIH activity.
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(as it appears on PubMed at http://www.pubmed.gov), where 12432100 is the PubMed ID number.
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{{ABSTRACT_PUBMED_12432100}}
==About this Structure==
==About this Structure==
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[[Category: III, C E.Dann.]]
[[Category: III, C E.Dann.]]
[[Category: Beta-jellyroll]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 01:53:47 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 15:18:33 2008''

Revision as of 12:18, 27 July 2008

Image:1mzf.png

Template:STRUCTURE 1mzf

Human Factor inhibiting HIF (FIH1) in Complex with 2-oxoglutarate

Template:ABSTRACT PUBMED 12432100

About this Structure

1MZF is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Structure of factor-inhibiting hypoxia-inducible factor 1: An asparaginyl hydroxylase involved in the hypoxic response pathway., Dann CE 3rd, Bruick RK, Deisenhofer J, Proc Natl Acad Sci U S A. 2002 Nov 26;99(24):15351-6. Epub 2002 Nov 13. PMID:12432100

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